Metabotropic glutamate receptors: targets for therapy of cerebral ischaemia

Several pathophysiological processes are involved in the progression of the cerebral ischaemic injury, among which are inflammation, peri-infarct depolarisation, apoptosis and excitotoxicity. Overactivation of glutamate receptors, both ionotropic and metabotropic, constitutes the central step in the excitotoxic cascade of events leading to neuronal cell death following acute brain ischaemia. Owing to their peculiar characteristics of modulatory receptors and due to their wide molecular and biological diversity, metabotropic glutamate receptors constitute an attractive target for the development of potential neuroprotective agents. Recent achievements in developing novel chemical entities and in the characterisation of the physiological and pathological role of individual metabotropic glutamate receptors in postischaemic degeneration will be reviewed.